Drospirenone safer than levonorgestrel when co-administered with psychotropics

For women using contraceptives while on psychotropic drugs, the risk of adverse events (AEs) appears to be lower with drospirenone than with levonorgestrel, whereas contraceptive failure is uncommon across progestins, according to a real-world study.

Researchers pooled data from four large prospective multinational cohort studies involving women with a new prescription of combined oral contraceptives (COC) and concomitant psychotropic drug use across the US and 13 European countries.

The frequency of contraceptive failures and AEs within 6 months of COC initiation was assessed by progestin type. Analyses were conducted using Poisson regression. Propensity score estimation was performed based on multiple covariates including age, BMI, smoking, medical history, history of hormonal contraceptive use, and education level.

A total of 7,679 COC users reporting psychotropic drug use at baseline were included in the analysis. Drospirenone (30.0 percent) was the most common progestin type, followed by norethisterone acetate/norethindrone acetate (20.5 percent), levonorgestrel (17.3 percent), norgestimate (11.6 percent), norethindrone (5.7 percent), nomegestrol/nomegestrol acetate (5.6 percent), desogestrel (4.9 percent), and dienogest (4.4 percent).

Within the first 6 months of follow-up, 39 (0.5 percent) contraceptive failures and 156 (2.0 percent) AEs were documented. Head-to-head comparison of different progestins against levonorgestrel showed a significantly lower risk of AEs with drospirenone (weighted incidence rate ratio, 0.5, 95 percent confidence interval, 0.3–0.9). No difference was observed for other progestins.

The study provides real-world evidence on potential drug interactions, which can inform future updates of evidence-based guidelines on contraception.